The present invention relates to an apparatus for inducing transient thermal gradients in human or animal tissue, and for obtaining infrared spectra from the tissue as the thermal gradient propagates through the tissue. The resulting infrared spectra may then be used to determine concentration of substances (analytes) present in the tissue, for example, glucose.
Millions of diabetics draw blood daily to determine blood glucose levels. Substantial effort has been expended in a search for a non-invasive method of accurately determining blood glucose concentrations. To that end, Optiscan Biomedical Corporation of Alameda, Calif., has significantly advanced the state of the art of non-invasive blood glucose analysis. In a series of patents and patent applications, Optiscan has defined the state of the art for non-invasive blood glucose determination.
The methodologies taught in U.S. patent application Ser. Nos. 08/820,378 and 09/267,121 may be performed by the apparatuses taught in U.S. patent application Ser. Nos. 08/816,723 and 09/265,195, and each of these references is hereby incorporated by reference.
By way of introduction, objects at temperatures greater than xe2x88x92273.16xc2x0 C. (absolute zero) emit infrared energy. Such emissions are often described by Planck""s Equation and referred to as xe2x80x9cblack body curvesxe2x80x9d. Theoretically, a body having an emissivity of 1.0 shows perfect agreement with Planck""s Equation. Advantageously, many objects have emissivity close to 1.0. In particular, human tissue has emissivity of approximately 0.9 to 0.98. It is well known that infrared emissions from the human body may be closely approximated by Planck""s Equation and yield black body type emission spectra.
Although the human body emits energy having a distribution that approximates that described by Planck""s Equation, Planck""s Equation does not completely describe the sum total of all energy emitted by a human body. Variations from perfect agreement with Planck""s Equation are caused by selective absorption of radiation by the layers of tissue and body fluid in the human body. Thus, layers of tissue and blood or other fluids may selectively absorb emitted energy from the deeper layers of the body before that energy can reach the surface of the skin. Furthermore, because the deeper layers of the human body are warmer than the outer layers, a temperature gradient exists within the body. This causes a further deviation from theoretical black body radiation emission.
However, the inventors have determined that, when the above two conditions exist, a composition-dependent absorption spectra may be constructed from proper analysis of the total energy emitted from the body. For heterogeneous bodies, the composition of matter may be depth dependent and, conversely, absorption spectra generated from deeper layers may contain sufficient composition information to allow accurate determinations of concentration of the individual constituents present in the tissue. This is possible when a temperature gradient either occurs naturally, or is induced in the body.
The invention taught in U.S. patent application Ser. No. 08/820,378 (""378) uses the naturally occurring body temperature as the source of infrared emissions. As these infrared emissions, which have emanated from deeper inside the body, pass through layers of tissue that are closer to the surface, certain wavelengths of energy are selectively absorbed by the intervening tissue. This selective absorption of signal produces bands of reduced energy in the expected emission spectra when the energy finally exits the material under study. This spectra is referred to as the absorption spectra of the material.
The invention taught in U.S. patent application Ser. No. 08/816,723 (""723) uses actively induced cooling to promote the selective absorption of radiation by causing a temperature gradient to propagate to selected layers of tissue, which typically range between 40 and 250 xcexc below the tissue surface. As explained in the ""723 application, absorption spectra of the tissue may be measured and the determination of glucose concentration may be made.
An additional technique for determining the concentration of substances (xe2x80x9canalytesxe2x80x9d) in a tissue sample is set forth in U.S. patent application Ser. No. 09/267,121 (""121). The ""121 application describes a method of measuring infrared emissions emitted by a tissue sample subject to a temperature gradient. By detecting emitted signals at selected wavelengths and comparing them to carefully selected reference signals, a frequency or a magnitude or a phase difference between the reference signal and an analytical signal may be used to determine analyte concentration. Furthermore, the method taught in the ""121 application teaches the use of an intermittently or periodically modulated temperature gradient and the continuing measurement of frequency, magnitude, or phase differences caused by analyte absorbance to determine analyte concentration. Furthermore, the ""121 application teaches a method of correcting for the effects caused by tissue surfaces.
According to U.S. patent application Ser. No. 08/820,378 (""378), there is provided a spectrometer for the non-invasive generation and capture of thermal gradient spectra from human or animal tissue. The ""378 spectrometer includes an infrared transmissive thermal mass for inducing a transient temperature gradient in the tissue by means of conductive heat transfer with the tissue, and a cooling means in operative combination with the thermal mass for cooling this thermal mass. There is also provided an infrared sensor for detecting infrared emissions emanating from the observed tissue as the gradient progresses into the tissue. Also included is a data capture means for sampling the output signals received from the sensor as the gradient progresses into the tissue. The ""723 invention uses a cooled germanium cylinder brought into intermittent contact with the test subject""s tissue. The resulting gradients are used to perform the methodology taught in Application ""378. Skin rewarming, according to this invention, is accomplished by simply allowing the patient""s skin to naturally rewarm after each cooling contact. Alternatively, rewarming may be accomplished by an external heat source in the form of a second warmer germanium cylinder. U.S. patent application Ser. No. 09/265,195 (""195) provides a xe2x80x9csolid-statexe2x80x9d apparatus for creating and measuring the effects of transient thermal gradients on tissue. The ""195 application teaches a single thermal mass structure (xe2x80x9ca thermal mass windowxe2x80x9d) which both heats and cools the tissue and is capable of transmitting the absorption spectra generated by the gradient. This allows the window to remain in contact with the tissue during the entire time measurements are made, thereby improving accuracy and measurement repeatability.
The inventors discovered that by inducing a cyclic temperature gradient certain measurement advantages accrue. These advantages are more apparent when a fairly rapid cooling/rewarming cycle time (hereinafter referred to as xe2x80x9ccycle timexe2x80x9d) is used. Cycle times on the order of 2 Hz are preferred. Existing devices encountered some difficulties obtaining the requisite cycle times due to residual heat or cooling remaining in the thermal mass structures after heating and cooling steps. Thus, it took excessive time and energy to cyclically induce the cooling and heating steps. There is a need for a thermal gradient device that can induce temperature gradients more quickly and using less energy. An advantage of devices which generate gradients using less energy is that smaller devices may be constructed.
According to the principles of the present invention there is provided a solid-state device for determining analyte concentrations within sample tissues. The device generates a thermal gradient in the tissue and measures infrared radiation spectra to make determinations of tissue analyte concentration. The device comprises an infrared transmissive window assembly having a plurality of infrared transmissive elements, one of which being a heating element, another being an insulating element. The device also has a cooling element in operative combination with the insulating element. The device also comprises an infrared detector for detecting an infrared radiation spectrum as it passes through said window assembly.
An important aspect of the invention is a thermal insulating and impedance matching element positioned between the heating and cooling elements. Yet another embodiment of the invention enhances the ability of the device to rapidly cycle through the cooling/rewarming cycle by including a heat sink in thermal contact with the cooling element. This effectively stabilizes the temperature in the device during cycling. This heat stability is enhanced through the use of a phase change material.
Other features of the invention are disclosed or apparent in the section entitled xe2x80x9cDETAILED DESCRIPTION OF THE INVENTIONxe2x80x9d.